title: Crystal structure of the Saccharomyces cerevisiae phosphatidylinositol-transfer protein.
abstract: The yeast phosphatidylinositol-transfer protein (Sec14) catalyses exchange of phosphatidylinositol and phosphatidylcholine between membrane bilayers in vitro. In vivo, Sec14 activity is essential for vesicle budding from the Golgi complex. Here we report a three-dimensional structure for Sec14 at 2.5 A resolution. Sec14 consists of twelve alpha-helices, six beta-strands, eight 3(10)-helices and has two distinct domains. The carboxy-terminal domain forms a hydrophobic pocket which, in the crystal structure, is occupied by two molecules of n-octyl-beta-D-glucopyranoside and represents the phospholipid-binding domain. This pocket is reinforced by a string motif whose disruption in a sec14 temperature-sensitive mutant results in destabilization of the phospholipid-binding domain. Finally, we have identified an unusual surface helix that may play a critical role in driving Sec14-mediated phospholipid exchange. From this structure, we derive the first molecular clues into how a phosphatidylinositol-transfer protein functions.
authors.affiliation: Center for Macromolecular Crystallography, Department of Microbiology, University of Alabama at Birmingham, 35294, USA.
authors.forename: B
authors.initials: B
authors.lastname: Sha
authors.forename: S E
authors.initials: SE
authors.lastname: Phillips
authors.forename: V A
authors.initials: VA
authors.lastname: Bankaitis
authors.forename: M
authors.initials: M
authors.lastname: Luo
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008565:Membrane Proteins; D008958:Models, Molecular; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; C483438:SEC14 protein, S cerevisiae; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins